The aim of the project is to clarify if G-protein is involved in the regulation of TGF-beta-induced extracellular matrix. Normal rat kidney (NRK) cells were incuvated for 24 h in the presence or absence of various concentration of TGF-beta. TGF-beta increased fibronectin accumulation in the supernatant in a dose-dependent manner without stimulation of cell proliferation. Moreover, 100 nM pertussis toxin (PTX) did not inhibit this effect. Therefore, we speculated that TGF-beta-induced fibronectin accumulation might be linked to PTX-insensitive G-protein. We systhesized several tipes of peptides which were cytoplasmic domains of several types of Galpha-subunits, according to Nishimoto's motif (J.Biol.Chem.269 ; 13756,1994). 22 amino acids (NNIQVVEDAVTDIIIANNLRC) indicating cytoplasmic domain of Goalpha inhibited 500 pM of TGF-beta increased fibronectin accumulation with IC50 of 1 muM.These results suggest that PTX-insensitive Go is involved in the TGF-beta-induced fibronectin accumulation.